Streptococci are important integral components of the microbial biofilm that is present on the surface of oral tissues and are intimately involved in the dynamic processes that govern the establishment, growth and control of this biofilm. Their interactions with salivary proteins are important for initiating bacterial colonization of oral tissues and their subsequent interactions with other oral microbes contribute to the maturation of plaque. Many of these reactions are mediated by a family of related streptococcal proteins collectively known as the antigen I/II polypeptides. However, the mechanisms defining antigen I/II interactions with human and bacterial components in the oral cavity and their relationships and contributions to oral diseases are not fully understood. The goals of this proposal are to understand how the function of antigen I/II proteins differ among species of oral streptococci, how the structure of the antigen I/II polypeptide influences its function, and how the structure and activities of antigen I/II proteins are affected by the oral environment. To accomplish these goals, the Principal Investigator will determine if the expression of multiple antigen I/II proteins by streptococci results in a tighter association of these organisms with oral tissues. He will correlate specific structural characteristics of different antigen I/II proteins with their functions. In addition, studies are proposed to determine if antigen I/II functions as a dimer and if the environment within the oral cavity affects antigen I/II function by influencing the stability of the dimer interface. An understanding of how antigen I/II contributes to the initiation and growth of the oral microbial biofilm will lead to a better understanding of how pathogenic organisms become established in the oral cavity and how minor structural differences that occur within related groups of proteins can dramatically influence their function. Finally, understanding the higher order structure of the antigen I/II proteins may lead to the development of broad spectrum anti-microbial agents that function by disrupting specific protein- protein interactions.